A major scientific challenge is to understand the molecular events that drive the evolution of premalignant lesions in actual tissue. Laser capture microdissection (LCM) was originated to provide a reliable method to procure pure populations of cells from specific microscopic regions of tissue sections; in one step, under direct visualization. The cells of interest are transferred to a polymer film that is activated by laser pulses. The exact morphology of the procured cells (with intact DNA, RNA and proteins) is retained and held on the transfer film. LCM technology has been successfully applied to DNA, and RNA analysis from frozen and fixed embedded tissue. In the past it has not been possible to extract, quantify and characterize the functional state of specific proteins expressed by individual subpopulations of cells in actual tissue. Consequently, an important ongoing and future goal is to extend our microdissection technology to include the molecular profiling of cancer progression into the realm of quantitative proteomics: characterization of known proteins, as well as discovery of new proteins associated with progression. We have developed reverse phase protein microarrays and have used them to correlate the state of signal pathways associated with response to experimental therapy. The ultimate goal is to individualize therapy based on a tumor molecular profile of the signal network.